Epigallocatechin gallate (EGCG), one of the major catechins found in green tea, was suggested to play a role as a chemopreventive agent in various human cancer models. In this study, we reported that EGCG has a profound antitumor effect on human tongue carcinoma cells by directly regulating glycolysis. EGCG dose-dependently inhibited anchorage-independent growth and short-term EGCG exposure substantially decreased EGF-induced EGF receptor (EGFR), Akt and ERK1/2 activation, as well as the downregulation of hexokinase 2 (HK2). Furthermore, inhibition of EGCG‑mediated HK2 expression was involved in Akt, but not in ERK1/2 signaling pathway suppression. Overexpression of constitutively activated Akt1 rescued inhibition of EGCG‑induced glycolysis. Moreover, EGCG inhibited HK2 expression on mitochondrial outer membrane and induced apoptosis. In summary, the results suggested that EGCG or a related analogue, may have a role in the management of human tongue carcinoma.